This project is designed to determine the mechanisms by which mycoplasmas cause animal and human disease in particular emphasizing their arthritogenic properties. Both in vitro and in vivo approaches will be made. In vitro studies will be conducted to define the mechanisms by which mycoplasmas activate normal mouse lymphocytes and to determine the collaborative role played by macrophages. In vitro studies will be conducted to determine the mechanisms of acute and chronic inflammation of mice, rats and rabbits induced by M. arthritidis and to define the reasons for the differing responses that are seen in these hosts. Evasion or enhancement of immune responses and immune complex deposition in articular tissues will be studied. Additional studies will be conducted to elucidate the potential role or mycoplasmas in acute human arthropathies as well as in rheumatoid arthritis.